Endocrine Abstracts

Introduction: Pheochromocytoma is a rare, usually benign tumor composed of neuroendocrine (chromaffin) cells of the adrenal medulla. It is the cause of secondary arterial hypertension. The biochemical diagnosis of a pheochromocytoma is based on the determination of concentration/excretion of catecholamine metabolites in blood or urine. The most sensitive biomarkers in the biochemical diagnosis of pheochromocytoma are plasma free methanephrines (metanephrine, normetanephrine and 3-methoxytyramine) assayed with chromatography tandem mass spectrometry (LC-MS/MS). Neuroendocrine cells have the ability to produce various proteins and neuropeptides, which, together with catecholamines, are released into the blood and can be designated as so-called circulating tumor markers.

Purpose: The aim of the study was to assess the usefulness of the determination of levels of selected Granin family proteins and INSM-1 (Insulinoma-associated protein 1) in the diagnosis of patients with pheochromocytoma.

Material and methods: Patients were divided into 4 groups:

1. Patients with pheochromocytoma (n=39),

2. Patients with incidentaloma (n=20),

3. Patients with primary arterial hypertension (n=20),

4. Control group – healthy volunteers (n=40).

The following biochemical determinations were performed in all patients: plasma levels of metanephrine, normetanephrine and 3-methoxytyramine, concentration of chromogranin B (CgB), proSAAS, INSM-1, chromogranin A (CgA) and derivates peptides: Pancreastatin/chromogranin A (250-301), Serpinin/prepro-chromogranin A (429-454), WE-14/prepro-chromogranin A (342-355) and Catestatin. Biochemical determinations were made using the LC-MS/MS technique with various immunochemical techniques (RIA, IRMA, ELISA).

Results: In patients with adrenal pheochromocytoma levels of: CgA, WE-14 and Catestanin were significantly different (P<0.001) compared to control groups (adenoma, hypertension and healthy subjects). The concentration of INSM-1 was significantly higher (P< 0.001) in patients with pheochromocytoma compared to the group of healthy people. In the group of patients with pheochromocytoma, the following indicators of the diagnostic value of the analyzed biomarkers were obtained: CgA: 82% sensitivity and 100% specificity (AUC 0,930); CgB: 87% sensitivity and 77% specificity (AUC 0,885); WE-14: 90% sensitivity and 95% specificity (AUC 0,959); Catestatin: 80% sensitivity and 92% specificity (AUC 0,903); Pancreastatin: 80% sensitivity and 95 specificity (AUC 0,913); proSAAS: 82% sensitivity and 67% specificity (AUC 0,760); INSM-1: 97% sensitivity and 100% specificity (AUC 0,976).

Conclusion: Determination of biomarkers: CgA, WE-14, Catestatin and INSM-1 had the highest diagnostic value in patients with pheochromocytoma.